Dapoxetine and its enantiomers are potent selective serotonine reuptake inhibitors (SSRIs) useful in the treatment of variety of diseases such as premature ejaculation, which is most common in men and other disorders like depression. Dapoxetine, a compound structurally related to the antidepressant fluoxetine (Prozac) is enantiomerically pure and one of the important drugs as an serotonin reuptake inhibitor. Dapoxetine is under phase III clinical trials in the United States, and it is approved as dapoxetine hydrochloride in various European countries for the indication of premature ejaculation and is marketed by Johnson & Johnson under the brand name PRILIGY. Dapoxetine hydrochloride is chemically described as (S)-N,N-dimethyl-3-(naphthalen-1-yloxy)-1-phenylpropan-1-amine hydrochloride (herein after referred by its generic name dapoxetine) which is represented by the structural formula:

European Patent No. 0,288,188 B1 (U.S. Pat. No. 5,135,947) describes 1-phenyl-3-napthalenyloxy propanamines derivatives including dapoexetine or a stereoisomer or a salt thereof, a pharmaceutical composition and method of treatment.
The EP'188 patent discloses a process for the preparation of enantiomerically pure S-(+)-dapoxetine as an oil and addition salts, by treating with inorganic acids such as hydrochloric acid, as well as, organic acids, such as oxalic acid, tartaric acid and p-toluene sulfonic acid.
U.S. Pat. No. 5,292,962 discloses a process for the preparation of S(+) dapoxetine and its acid addition salts by treating with inorganic acids such as hydrochloric acid.
Shafi A. Siddiqui et al Tetrahydron Asymmetry 17 (2006) 860-866 and Tetrahydron: Asymmetry 18 (2007) 2099-2103 describes a process for the preparation of S-(+)-dapoxetine as a colorless oil.
PCT application publication WO 2008035358A2 describes a process for the preparation of S(+) dapoxetine by resolution of racemic (±)-dapoxetine using (+)-di-p-toluoyl tartaric acid as a resolving agent to obtain S(+)-dapoxetine and its salts.
The aforementioned processes dealt only about the preparation of racemic dapoxetine and dapoxetine S(+)enantiomer in the form of an oil and as crude residues which are impure.
The discovery of solid states of intermediates of a pharmaceutically useful compound, like dapoxetine hydrochloride, provides an opportunity to improve the performance characteristics of a pharmaceutical product. Thus, it enlarges the repertoire of the materials that a formulation scientist has available for designing, for example, a pharmaceutical dosage form of a drug with a targeted release profile or other desired characteristic.
The racemic dapoxetine and dapoxetine S(+)enantiomer in the solid form is not reported in the art.
Now, racemic dapoxetine and dapoxetine S(+)-enantiomer as solids have been discovered.
The present invention relates to the solid state properties of racemic dapoxetine and dapoxetine S(+)enantiomer. These properties can be influenced by controlling the conditions under which racemic dapoxetine and dapoxetine S(+)enantiomer are obtained in solid form.
Solid state physical properties include, for example, the flowability, compaction and solubility, which eases the handling and processing of the final pharmaceutical product.
The solid form of a compound may also affect its behavior on compaction and its storage stability.
These practical physical characteristics are influenced by the conformation and orientation of molecules in the unit cell, which defines a particular polymorph of a compound which may give rise to distinct spectroscopic properties that may be detectable by XRPD, solid state 13C NMR spectroscopy, DSC and infrared spectrometry.
Additionally, types of multiple component solids that may potentially offer other property improvements for a pharmaceutical compound or salt thereof include for e.g., solvates) e.g., hydrates). See, e.g., Byrn et al., Solid state chemistry of drugs, supra.
The discovery of solid forms of intermediates of a pharmaceutically important product is of great importance in the development of a safe, effective, stable and marketable pharmaceutical compound.
Since the solid form of racemic dapoxetine and dapoxetinde S(+) enantiomer is obtained with high purity, it is hence more, suitable for pharmaceutically active compounds and their formulations. Also, the the solids will also will also be used to obtain highly pure pharmaceutically acceptable salts of dapoxetine.
Accordingly, there is thus an unmet need for solid forms of the intermediates, like racemic dapoxetine and dapoxetine S(+)enantiomer.
Now, we have invented and isolated racemic dapoxetine and dapoxetine S(+)enantiomer in solid forms which are obtained with high purity, and hence are more suitable for the preparation of the highly pure, final pharmaceutical product dapoxetine hydrochloride.